癌毒病机的生物学基础探讨
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摘要
肿瘤微环境是与肿瘤侵袭、转移密不可分的局部内环境,肿瘤生物学研究的最新进展凸显了肿瘤细胞来源外泌体在调控肿瘤微环境中的重要地位。创建中医肿瘤癌毒病机理论,提出癌毒是肿瘤发生、发展的关键病机,肿瘤微环境可能是癌毒病机理论的生物学基础。通过比较癌毒与肿瘤细胞来源外泌体的产生、致病特性与致病机制,认为癌毒与肿瘤细胞来源外泌体密切相关,肿瘤细胞来源外泌体可能是癌毒病机的生物学基础,对进一步揭示癌毒病机理论的科学内涵具有重要意义。
Tumor microenvironment is a local environment closely related to tumor cell proliferation and metastasis, recent advances in tumor biology research emphasize the important role of tumor cell-derived exosome in the regulation of tumor microenvironment. It is suggested that cancer toxin is the key pathogenesis of tumor occurrence and development, and tumor microenvironment may be the biological basis of cancer poison pathogenesis theory. By comparing the generation, pathogenic characteristics and pathogenic mechanism of cancer toxin and tumor cell-derived exosome, it is believed that cancer toxin is closely related to tumor cell-derived exosome, which may be the biological basis of cancer toxin and pathogenesis. It is of great significance to further revealing the scientific connotation of cancer virus pathogenesis theory.
Tumor microenvironment is a local environment closely related to tumor cell proliferation and metastasis, recent advances in tumor biology research emphasize the important role of tumor cell-derived exosome in the regulation of tumor microenvironment. It is suggested that cancer toxin is the key pathogenesis of tumor occurrence and development, and tumor microenvironment may be the biological basis of cancer poison pathogenesis theory. By comparing the generation, pathogenic characteristics and pathogenic mechanism of cancer toxin and tumor cell-derived exosome, it is believed that cancer toxin is closely related to tumor cell-derived exosome, which may be the biological basis of cancer toxin and pathogenesis. It is of great significance to further revealing the scientific connotation of cancer virus pathogenesis theory.
引文
[1] 程海波,沈卫星,吴勉华,等.基于肿瘤微环境的癌毒病机理论研究[J].南京中医药大学学报,2014,30(2):105-107.
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[5] 郑舞,杨金坤.肿瘤微环境及其中医病机[J].中医杂志,2015,56(20):1720-1724.
[6] 陆文秀.晚期胃肠道肿瘤血瘀程度与外周血肿瘤缺氧相关蛋白关系[J].中国实验方剂学杂志,2013,19(23):301-306.
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[14] CORCORAN C,RANI S,O'BRIEN K,et al.Docetaxel-resistance in prostate cancer:Evaluating associated phenotypic changes and potential for resistance transfer via exosomes[J].PLoS ONE,2012,7(12):e50999.
[15] MARTINS VR,DIAS MS,HAINAUT P.Tumor-cell-derived microvesicles as carriers of molecular information in cancer[J].Curr Opin Oncol,2013,25(1):66-75.
[16] CARISSIMI C,CARUCCI N,COLOMBO T,et al.miR-21 is a negative modulator of T-cell activation[J].Biochimie,2014,107:319-326.
[17] DUNAND-SAUTHIER I,SANTIAGO-RABER ML,CAPPONI L,et al.Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function[J].Blood,2011,117(17):4490-4500.
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[19] LI W,KONG L B,LI J T,et al.MiR-568 inhibits the activation and function of CD4+ T cells and Treg cells by targeting NFAT5[J].Int Immunol,2014,26(5):269-281.
[20] LIU C,YU S,ZINN K,et al.Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function[J].J Immunol,2006,176(3):1375-1385.
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[23] SKOG J,WURDINGER T,VAN RIJN S,et al.Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers[J].Nat Cell Biol,2008,10(12):1470-1476.
[24] TADOKORO H,UMEZU T,OHYASHIKI K,et al.Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells[J].J Biol Chem,2013,288(48):34343-34351.
[25] SUBRA C,GRAND D,LAULAGNIER K,et al.Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[J].J Lipid Res,2010,51(8):2105-2120.
[26] ATRETKHANY KN,DRUTSKAYA MS,NEDOSPASOV SA,et al.Chemokines,cytokines and exosomes help tumors to shape inflammatory microenvironment[J].Pharmacol Ther,2016,168:98-112.
[27] WHITESIDE T L.Exosomes in cancer:Another mechanism of tumor-induced immune suppression[J].Adv Exp Med Biol,2017,1036:81-89.
[28] YIN Y,CAI X,CHEN X,et al.Tumor-secreted miR-214 induces regulatory T cells:A major link between immune evasion and tumor growth[J].Cell Research,2014,24(10):1164-1180.
[29] LOBB R J,LIMA L G,MOLLER A.Exosomes:Key mediators of metastasis and pre-metastatic niche formation[J].Semin Cell Dev Biol,2017,67:3-10.
[2] 程海波,王俊壹,李柳.癌毒病机分类及其在肿瘤临床治疗中的应用[J].中医杂志,2019,60(2):119-122.
[3] LOGOZZI M,CAPASSO C,DI RAIMO R,et al.Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity[J].J Enzyme Inhib Med Chem,2019,34(1):272-278.
[4] KING HW,MICHAEL MZ,GLEADLE JM.Hypoxic enhancement of exosome release by breast cancer cells[J].BMC Cancer,2012,12:421.
[5] 郑舞,杨金坤.肿瘤微环境及其中医病机[J].中医杂志,2015,56(20):1720-1724.
[6] 陆文秀.晚期胃肠道肿瘤血瘀程度与外周血肿瘤缺氧相关蛋白关系[J].中国实验方剂学杂志,2013,19(23):301-306.
[7] 程海波,吴勉华.周仲瑛教授“癌毒”学术思想探析[J].中华中医药杂志,2010,25(6):866-869.
[8] RUIVO CF,ADEM B,SILVA M,et al.The biology of cancer exosomes:Insights and new perspectives[J].Cancer Res,2017,77(23):6480-6488.
[9] CAMUSSI G,DEREGIBUS MC,TETTA C.Tumor-derived microvesicles and the cancer microenvironment[J].Curr Mol Med,2013,13(1):58-67.
[10] 程海波.癌毒病机理论探讨[J].中医杂志,2014,55(20):1711-1715.
[11] WANG Z,CHEN JQ,LIU JL,et al.Exosomes in tumor microenvironment:novel transporters and biomarkers[J].J Transl Med,2016,14(1):297.
[12] WELTON JL,KHANNA S,GILES PJ,et al.Proteomics analysis of bladder cancer exosomes[J].Mol Cell Proteomics,2010,9(6):1324-1338.
[13] AL-NEDAWI K,MEEHAN B,MICALLEF J,et al.Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells[J].Nat Cell Biol,2008,10(5):619-624.
[14] CORCORAN C,RANI S,O'BRIEN K,et al.Docetaxel-resistance in prostate cancer:Evaluating associated phenotypic changes and potential for resistance transfer via exosomes[J].PLoS ONE,2012,7(12):e50999.
[15] MARTINS VR,DIAS MS,HAINAUT P.Tumor-cell-derived microvesicles as carriers of molecular information in cancer[J].Curr Opin Oncol,2013,25(1):66-75.
[16] CARISSIMI C,CARUCCI N,COLOMBO T,et al.miR-21 is a negative modulator of T-cell activation[J].Biochimie,2014,107:319-326.
[17] DUNAND-SAUTHIER I,SANTIAGO-RABER ML,CAPPONI L,et al.Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function[J].Blood,2011,117(17):4490-4500.
[18] CURTALE G,CITARELLA F,CARISSIMI C,et al.An emerging player in the adaptive immune response:microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes[J].Blood,2010,115(2):265-273.
[19] LI W,KONG L B,LI J T,et al.MiR-568 inhibits the activation and function of CD4+ T cells and Treg cells by targeting NFAT5[J].Int Immunol,2014,26(5):269-281.
[20] LIU C,YU S,ZINN K,et al.Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function[J].J Immunol,2006,176(3):1375-1385.
[21] 周仲瑛,程海波,周学平,等.中医药辨治肿瘤若干理念问题的探讨[J].南京中医药大学学报,2014,30(2):101-104.
[22] ZHAO H,YANG L,BADDOUR J,et al.Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism[J].Elife,2016,5:e10250.
[23] SKOG J,WURDINGER T,VAN RIJN S,et al.Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers[J].Nat Cell Biol,2008,10(12):1470-1476.
[24] TADOKORO H,UMEZU T,OHYASHIKI K,et al.Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells[J].J Biol Chem,2013,288(48):34343-34351.
[25] SUBRA C,GRAND D,LAULAGNIER K,et al.Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[J].J Lipid Res,2010,51(8):2105-2120.
[26] ATRETKHANY KN,DRUTSKAYA MS,NEDOSPASOV SA,et al.Chemokines,cytokines and exosomes help tumors to shape inflammatory microenvironment[J].Pharmacol Ther,2016,168:98-112.
[27] WHITESIDE T L.Exosomes in cancer:Another mechanism of tumor-induced immune suppression[J].Adv Exp Med Biol,2017,1036:81-89.
[28] YIN Y,CAI X,CHEN X,et al.Tumor-secreted miR-214 induces regulatory T cells:A major link between immune evasion and tumor growth[J].Cell Research,2014,24(10):1164-1180.
[29] LOBB R J,LIMA L G,MOLLER A.Exosomes:Key mediators of metastasis and pre-metastatic niche formation[J].Semin Cell Dev Biol,2017,67:3-10.